慢性活动性乙型肝炎患者细胞免疫功能检测及其临床意义

测定了例慢性活动乙型肝炎患者外周血单个核细胞（ＰＢＭＣ）产生的白细胞介素２（ＩＬ－２）活性，其中部分病人检测了血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平，膜白细胞介素２受体（ｍＩＬ－２Ｒ）表达，ＬＡＫ活性及外周血Ｔ淋巴细胞亚群，并分析了它们之间的相关性，结果表明：ＩＬ－２活性，ｍＩＬ－２Ｒ表达，ＬＡＫ活性，ＣＤ４／ＣＤ８比值显著低于正常对照组（Ｐ〈０．００１），而ｓＩＬ－２Ｒ水平，ＣＤ８细胞显     

白癜风患者外周血T淋巴细胞异常活化

本文以人类白细胞抗原ＤＲ位点（ＨＬＡ－ＤＲ）及白细胞介素２受体亚单位Ｐ５５和Ｐ７５（ＩＬ－２Ｒ，Ｐ５５和ＩＬ－２Ｒ，Ｐ７５）的表达为Ｔ淋巴细胞活化的指标，用双色免疫标记流式细胞法对白癜风患者外周血Ｔ淋巴细胞（ＶＰＢＴＬ）进行分析。实验发现：ＨＬＡ－ＤＲ在ＶＰＢＴＬ及其亚群Ｔ辅助细胞（Ｔｈ，ＣＤ４＾＋细胞）和Ｔ抑制细胞（Ｔｓ，ＣＤ８＾＋细胞）的表达均明显高于正常人，分别为：４９．６２％比１４．５４％     

新生儿肺炎血清sIL—2R与外周血单个核细胞IL—2R表达的研究

为了解新生儿肺炎ＩＬ－２Ｒ的变化，采用ＥＬＩＳＡ法检测３３例新生儿肺炎血清ｓＩＬ－２Ｒ水平、ＰＢＭＣ体外ＰＨＡ培养７２小时ｍＩＬ－２Ｒα表达及上清液ｓＩＬ－２Ｒ水平，并与３６例正常新生儿对照。结果：（１）患儿血清ｓＩＬ－２Ｒ水平治疗前高于治疗后（Ｐ〈０．００１），且治疗前后均高于对照（Ｐ〈０．０１）；治疗前血清ｓＩＬ－２Ｒ水平与病情轻重密切相关（Ｐ〈０．０１）；（２）患儿ｍＩＬ－２Ｒα表达治疗前后     

智能低下患儿外周血T淋巴细胞亚群与sIL－2R水平的变化

本文检测５５例智能低下（ＭＲ）患儿及正常人外周血Ｔ淋巴细胞亚群及血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）的水平，结果表明ＭＲ患儿ＣＤ３＋、ＣＤ４＋细胞显著低于对照组，ＣＤ８＋细胞明显高于对照组，ＣＤ４＋／ＣＤ８＋比值下降。ｓＩＬ－２Ｒ活性明显高于对照组。     

sIL—2R释放与T细胞活化的相关性研究

本实验利用双抗体夹心ＥＬＩＳＡ、流式细胞测量术及淋巴细胞增殖试验观察了可溶性ＩＬ－２受体（ｓＩＬ－２Ｒ）释放与细胞膜ＩＬ－２受体（ｍＩＬ－２Ｒ）表达及淋巴细胞增殖反应的相关性。结果显示：①在不更换培养液的情况下，ＰＨＡ刺激的淋巴细胞培养上清中的ｓＩＬ－２Ｒ释放与ｍＩＬ－２Ｒ表达在７２ｈ内呈正相关（ｒ＝０．９４，Ｐ〈０．０５），之后，ｍＩＬ－２Ｒ的表达逐渐减少，而ｓＩＬ－２Ｒ水平则继续缓慢增加，呈负     

可溶性IL－2R在选择性IgA缺乏症发病机理中的意义

白细胞介素２（ＩＬ－２）及其受体（ＩＬ－２Ｒ）系统在机体免疫调节中发挥着重要作用。本研究首先以间接免疫荧光技术检测了选择性ＩｇＡ缺乏症（ＳＩｇＡＤ）患儿活化淋巴细胞膜表面白细胞介素２受体（ｍＩＬ－２Ｒα）的表达情况及其Ｔ细胞亚类水平，继而采用双抗体夹心ＥＬＩＳＡ法检测了ＳＩｇＡＤ患儿血清可溶性白细胞介素２受体（ＳＩＬ－２Ｒα）的含量。结果表明：ＳＩｇＡＤ患儿组的Ｔａｃ阳性细胞百分率（ｍＩＬ－２Ｒα）明显高于正常对照组，其ＣＤ４＋细胞百分率明显低于正常对照组、ＣＤ８＋细胞百分率明显高于正常对照组。而其血清ＳＩＬ－２Ｒα含量亦明显高于正常对照组。研究显示：ＳＩｇＡＤ患儿ｍＩＬ－２Ｒα的表达虽高于正常对照组，但因其Ｔ细胞亚类的显著异常既有体内存在着明显的细胞免疫功能的损害，导致ＩＬ－２的生成不足，使高水平的ＳＩＬ－２Ｒα大量脱落成为ＳＩＬ－２Ｒα，而ＳＩＬ－２Ｒα又可与ＳＩＬ－２Ｒα竞争结合ＩＬ－２，从而使机体细胞免疫功能的损害进一步加剧。     

智能低下患儿外周血T淋巴细胞亚群与sIL—2R水平的变化

本文检测５５例智能低下（ＭＲ）患儿及正常人外周血Ｔ淋巴细胞亚群及血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）的水平，结果表明ＭＲ患儿ＣＤ３＾＋、ＣＤ４＾＋细胞显著低于对照组，ＣＤ８＾＋细胞明显高于对照组，ＣＤ４＾＋／ＣＤ８＾＋比值下降。ｓＩＬ－２Ｒ活性明显高于对照组。     

SLE患者T细胞和IL－2／IL－2R系统变化的临床意义

本文检测３７例（４１份）ＳＬＥ患者ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、ｓＩＬ－２Ｒ水平、淋巴细胞转化及Ｔ细胞亚群。结果表明：ＳＬＥ患者ｓＩＬ－２Ｒ水平升高，而ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、淋转率、ＣＤ４＋百分率和ＣＤ４＋／ＣＤ８＋比值均下降，由于其中仅有ｓＩＬ－２Ｒ水平与疾病活动性有关，因而ｓＩＬ－２Ｒ可作为疾病活动的一个指标。免疫指标的变化与激素治疗无关。本文认为Ｔ细胞功能及ＩＬ－２释放紊乱主要是由疾病本身的免疫调节紊乱引起。     

IL－2R水平在骨髓增生异常综合征中的意义

为了对ＭＤＳ的发生发展和免疫学异常进一步了解，我们用双抗体夹心ＥＬＩＳＡ法检测２０例ＭＤＳ患者血清中ｓＩＬ－２Ｒ水平；采用ＡＰＡＡＰ桥联酶免疫染色观察９例ＭＤＳ患者ＰＢＭＣ中ｍＩＬ－２Ｒ的表达，发现ＭＤＳ患者血清中ｓＩＬ－２Ｒ较正常人增高。在ＭＤＳ亚型中ＲＡＥＢ，ＲＡＥＢ－ｔ组较ＲＡ组增高显著，Ｐ＜０．０１；校再障组也增高。ｍＩＬ－２Ｒ阳性细胞百分率也较正常人高。血清中ｓＩＬ－２Ｒ释放水平与ＰＢＭＣ中ｍＩＬ－２Ｒ的表达比较，两者无明显相关。研究结果表明，ＭＤＳ除髓系细胞累及外，ＩＬ－２Ｒ水平增高可能是ＭＤＳ淋巴细胞异常，免疫系统功能紊乱的一种表现。     

SLE患者T细胞和IL－2／IL－2R系统变化的临床意义

本文检测３７例（４１份）ＳＬＥ患者ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、ｓＩＬ－２Ｒ水平、淋巴细胞转化及Ｔ细胞亚群。结果表明：ＳＬＥ患者ｓＩＬ－２Ｒ水平升高，而ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、淋转率、ＣＤ４＋百分率和ＣＤ４＋／ＣＤ８＋比值均下降，由于其中仅有ｓＩＬ－２Ｒ水平与疾病活动性有关，因而ｓＩＬ－２Ｒ可作为疾病活动的一个指标。免疫指标的变化与激素治疗无关。本文认为Ｔ细胞功能及ＩＬ－２释放紊乱主要是由疾病本身的免疫调节紊乱引起。     

Soluble interleukin 2 receptor release, interleukin 2 production, and interleukin 2 receptor expression in activated T-lymphocytes in vitro.

Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL2R). The present study was undertaken to define the proportion of T lymphocyte subsets that express the IL2R (CD25 antigen) upon different mitogenic stimulation. Double immunofluorescence staining with different fluorochromes, fluorescein isothiocyanate and phycoethyrin, was applied for identification of IL2R positive cells and individual lymphocyte subset. The exact percentage of individual activated lymphocyte subset bearing IL2R was enumerated by photographic counting. There was paucity of IL2R in freshly isolated, unstimulated peripheral blood, PBMC cultured without mitogen, and cultured B lymphocytes. Following pokeweed mitogen stimulation in vitro, 19% of CD4 (T-helper/inducer) lymphocytes and 14% of CD8 (T-suppressor/cytotoxic) lymphocytes expressed IL2R. Similarly, 25% of CD4 lymphocytes and 19% of CD8 lymphocytes expressed IL2R following phytohemagglutinin stimulation in vitro. Contrary to the reported data of Tac-positive cells in human lymphoid tissues, our study revealed that, upon lectin mitogen stimulation, approximately 55% of IL2R positive PBMC were CD4 lymphocytes, and 45% of them were CD8 lymphocytes. These observations imply the plausible notion that interleukin-2 mediated immune activation of T lymphocytes in PBMC is different from that in local lymphoid organs. It was also demonstrated that the release of soluble IL2R (sIL2R) and IL2 production in supernatant from cultured PBMC varied with different lectin stimulation. A significant correlation was demonstrated between the cellular and soluble IL2R but the production of IL2 from activated mononuclear cells bore no good correlation with either the cellular IL2R expression or the release of sIL2R.     

IL-2R反义S-ODNs抑制人淋巴细胞增殖及IL-2R表达

ＩＬ ２Ｒα、β、γｍＲＮＡ上起始密码子ＡＵＧ的下游序列, 合成与之互补的硫代反义寡聚脱氧核糖核酸（ＩＬ ２Ｒα、β、γＳ ＯＤＮｓ） , 长度为２０ｎｔ。实验结果表明,ＩＬ ２ＲαＳ ＯＤＮｓ 对外周血淋巴细胞生长最高抑制率可达到８１－９２％ ; 而ＩＬ ２ＲβＳ ＯＤＮｓ和ＩＬ ２ＲγＳ ＯＤＮｓ 的抑制作用较低, 其最高抑制率均为５９－１ ％ 。在１０μｍｏｌ／ＬＩＬ ２ＲαＳ ＯＤＮｓ 作用后的第４８ 小时,ｓＩＬ ２Ｒ 的表达下降８０％ ; ｍＩＬ ２Ｒα的表达下降５１－５％ 。     

T-lymphocyte activation in IgA nephropathy: Serum-soluble interleukin 2 receptor level,interleukin 2 production,and interleukin 2 receptor expression by cultured lymphocytes

The present study was undertaken to examine the T-lymphocyte activation in IgA nephropathy. Serum-soluble interleukin 2 receptor (sIL2R) levels were studied in 29 IgA nephritic patients, 17 patients with chronic glomerulonephritis (non-IgA nephropathy), and 30 healthy controls during an infection-free period. No difference in serum sIL2R level was demonstrated among these three groups of subjects. However, the serum sIL2R levels of IgA nephritic patient rose significantly during clinical exacerbation with synpharyngitic macroscopic hematuria and the serum sIL2R levels fell when hematuria subsided. Mitogen-stimulated cellular interleukin 2 receptor (IL2R) expression, sIL2R release, and interleukin 2 (IL2) production were also examined in peripheral blood mononuclear cells (PBMC) cultured for 24–48 hr in 21 patients with IgA nephropathy, 17 patients with chronic glomerulonephritides, and 17 healthy controls. The total cellular IL2R expression and sIL2R release did not differ among these three groups of subjects. However, the individual T-cell subsets bearing IL2R were distinctly different between IgA nephritic patients and the other two groups of controls. IgA nephritic patients had increased activated CD4+ lymphocytes and reduced activated CD8+ lymphocytes. Furthermore, IL2 production in response to phytohemagglutinin and pokeweed mitogen stimulation was increased in lymphocytes from patients with IgA nephropathy. The IL2 production did not correlate with the quantities of cellular and sIL2R yet the cellular IL2R expression paralleled the sIL2R released by cultured lymphocytes. Our present study suggests that the T lymphocytes from patients with IgA nephropathy have a defect in overproduction of IL2 and increased activated T helper-cell subset upon mitogenic stimulation. Serum measurement of sIL2R could potentially be useful in monitoring the disease activity.     

Sublingual immunotherapy alters expression of IL‐4 and its soluble and membrane‐bound receptors

Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL‐4, and its soluble and membrane‐bound receptor in patients with SAR before and after SIT. Using allergen‐challenge assays, we found that SIT treatment decreased IL‐4 cytokine levels, as previously reported. We also observed a significant decrease in the IL‐4 membrane‐bound receptor (mIL4R) at the level of both mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL‐4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications.     

大肠癌患者围手术期免疫状态变化的临床意义

目的 研究大肠癌患者围手术期的免疫状态。方法 应用ＡＰＡＡＰ夹心法ＥＬＩＳＡ和比色法分别测定大肠癌患者手术前后Ｔ细胞亚群变化,血浆可溶性白介２受体（ｓＩＬ－２Ｒ）及一氧化氮（ＮＯ）和癌组织的ＳＩＬ－２Ｒ,ＮＯ含量。结果 大谫ＣＤ３,ＣＤ４细胞、ＣＤ４／ＣＤ８比值和血浆ＮＯ水平明显低于正常,血浆ＳＩＬ－２Ｒ、ＣＤ８细胞较正常显著增高,肿瘤切除后３周左右ＣＤ３、ＣＤ４细胞、ＣＤ４／ＣＤ８和血浆术前有明     

A recombinant extracellular domain of the human interleukin 4 receptor inhibits the biological effects of interleukin 4 on T and B lymphocytes

Human interleukin 4 (IL4) acts on various hematopoietic cell types through interaction with a specific cell surface receptor (IL4R), whose cDNA has been cloned. We have produced a cDNA encoding a soluble form of the extracellular domain of the human IL 4R (sIL4R) and describe here the capacity of sIL4R to antagonize the in vitro activities of IL4 on normal B and T lymphocytes. sIL4R inhibited IL4-induced proliferation of both phytohemagglutinin-preactivated peripheral blood mononuclear cells (PBMC) and anti-IgM co-stimulated tonsil B cells with similar efficiency. This inhibitory activity was specific since sIL4R did not affect IL2-dependent proliferation of these cells. sIL4R also blocked IL4-dependent induction of the low-affinity receptor for IgE on B cells and inhibited IgE production by IL4-activated PBMC. Thus, in contrast to the IL6R extracellular domain which stimulates IL6 biological activity, the IL4R extracellular domain is a powerful antagonist of its specific ligand.     

Suppressive effect of Saibokuto on Dermatophagoides farinae (Df) antigen-induced IL2 responsiveness of lymphocytes from asthmatic children

The effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cells for induction of their IL2 responsiveness. The same dose of Saibokuto had no impact on non-adherent cells. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patients on stimulation wit PPD, but not with Con A. These combined data suggests that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children. Effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cell for induction of their IL2 responsiveness. Non-adherent cells had no impact by the same dose of Saibokuto. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patient on stimulation with PPD, but not Con A. These combined data suggest that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children. Effect of Saibokuto on induction of antigen specific IL2 responsiveness was studied. Saibokuto suppressed the induction of IL2 responsiveness induced by Dermatophagoides farinae (Df) antigen in peripheral blood mononuclear cells from patients with bronchial asthma. Saibokuto-pretreated adherent cells failed to present Df antigen to non-adherent responding T cell for induction of their IL2 responsiveness. Non-adherent cells had no impact by the same dose of Saibokuto. Saibokuto also suppressed the induced IL2 responsiveness of lymphocytes from the same patient on stimulation with PPD, but not Con A. These combined data suggest that Saibokuto has a weak immunosuppressive effect on Df induced IL2 responsiveness of lymphocytes from asthmatic children.     

Influence of hyposensitization on soluble interleukin-2 receptor, eosinophil cationic protein, in vitro lymphocyte proliferation, in vitro lymphocyte adhesion, and lymphocyte membrane markers in childhood asthma

Soluble interleukin-2 receptor (sIL-2R), eosinophil cationic protein (ECP), the lymphoproliferative response to house-dust mite (HDM), adhesion to human umbilical vein endothelial cells (HUVEC), and lymphocyte membrane markers were studied in three groups of children: healthy children, asthmatic children without hyposensitization (HS), and asthmatic children with HS. HS was associated with significantly lower numbers of peripheral blood eosinophils (PBE) and lower sIL-2R serum levels and with a tendency to lower ECP serum levels and lymphoproliferative response to HDM. There were no changes in the T-lymphocyte phenotypic markers CD4 and CDS among the three groups. The interleukin-2 receptor (IL-2R, CD25) on HDM-stimulated T lymphocytes increased over unstimulated T lymphocytes in the three groups. The CD25 expression was higher on HDM-stimulated lymphocytes in both asthmatic groups than in healthy children. Adhesion of lymphocytes on HUVEC increased significantly after HDM stimulation in asthmatic children without HS, whereas no change was observed in the two other groups. However, there was no change in the expression of adhesion molecules CD29 and CD1 la on lymphocytes in either of the groups. This study provides further evidence that HS can modify lymphocyte and eosinophil functions.     

A cytokine, lymphocyte blastogenesis inhibitory factor (LBIF), arrests mitogen-stimulated T lymphocytes at early G1 phase with no influence on interleukin 2 production and interleukin 2 receptor light chain expression

The function of a human cytokine, lymphocyte blastogenesis inhibitory factor (LBIF), was characterized. To this end, LBIF was purified from crude supernatant of U-937 cells, a human macrophage-like cell line, by using fast protein liquid chromatography (FPLC). We demonstrated here that (a) the LBIF preparation completely inhibited phytohemagglutinin (PHA)-stimulated T cell proliferation; (b) however, in PHA-stimulated T lymphocytes LBIF inhibited neither interleukin (IL)2 production nor the expression of IL2 receptor (IL2R) light chain (CD25) which play a critical role for T cell proliferation; (c) LBIF arrested PHA-stimulated T lymphocytes at the G1 phase of cell cycle and inhibited entry into S phase, thus inhibiting lymphocyte proliferation. Wright-Giemsa's staining of the cells showed that PHA/LBIF-stimulated cells were arrested in early G1. In agreement with this result, LBIF strongly inhibited PHA-induced RNA synthesis. Further, LBIF inhibited the induction of the transferrin receptor which is normally expressed at the late G1 phase of the cell cycle. The inhibitory activity of LBIF was reversible. Thus, this study elucidated that LBIF arrests PHA-stimulated T lymphocytes at a point between the stages of IL2 production or IL2R light chain expression (in early G1) and transferrin receptor expression (in late G1). Taken together, these results suggest that there might be a control system of T cell proliferation distinct from the previously reported mechanisms, such as the inhibition of IL2 production or the inhibition of IL2R light chain (CD25) expression, and that LBIF might be an important molecule in the regulation of normal lymphocyte proliferation.     

Step-down and step-up therapy in moderate persistent asthma

BACKGROUND: A step-down therapy may be more beneficial for the management of asthma than a step-up therapy. METHODS: Eighty-two asthmatic patients with moderate persistent asthma were enrolled in the study and randomized into three groups. One group of patients received 400 microg/day of beclomethasone dipropionate (BDP) for 4 weeks and then 800 microg/day for another 4 weeks (step-up group). The other two groups of patients received 1,200 microg/day of BDP for 4 weeks with or without short-term oral steroid (prednisolone, 0.5 mg/day for 1 week) and then 800 microg/day for another 4 weeks (step-down group). Severe exacerbation of asthma, asthma symptoms, respiratory function and rescue use of inhaled beta(2)-agonists were monitored. If asthma was well controlled, the dose of BDP was decreased every 3 months and if asthma was exacerbated, the dose of BDP was increased until 8 months after the initial treatment. RESULTS: Twenty-two patients during the run-in period, 4 patients in the step-up group, 2 patients in the step-down group treated with a high dose of BDP and no patients in the step-down group with oral steroids during first 4 weeks dropped out because of severe exacerbation of asthma. Although asthma symptoms and respiratory function significantly improved 8 weeks after the therapy in all groups, more significant and prompt improvements of these parameters were observed in patients of the step-down group than in patients of the step-up group after the first 2 weeks of treatment. Furthermore, step-down therapy with short-term oral steroid resulted in the lowest maintenance doses of BDP at 8 months of the three groups. CONCLUSIONS: These results suggest that step-down therapy starting with a high dose of inhaled steroid and short-term oral steroid is more effective in gaining prompt control of asthma and reducing the severe exacerbation of asthma and the maintenance dose of inhaled steroids than a step-up therapy starting with a low dose of inhaled steroids in patients with moderate persistent asthma.